The candidate received his B.S. degree from Louisiana State Univ. (1972, chemical engineering, magna cum laude) and M.D. degree from Johns Hopkins Univ. (1976). His postgraduate training was undertaken at University Hospitals of Cleveland (1976-80; internship and residency in internal medicine, clinical endocrine fellowship) and subsequently at Dartmouth-Hitchcock Medical Center, Hanover, NH (1980-present; chief medical resident, research fellow in endocrinology). His research experience to date has included investigations of thyroid hormone action in a human leukemic cell line and in the rat pituitary gland during fasting and hypothyroidism and following transplantation of the pituitary to the renal capsule. The long-term objective of the candidate's proposed research is to determine the specific interrelationships between thyroid hormone and other hormonal and metabolic factors in the control of anterior pituitary gland function. The proposed project focuses on the role of hypothalamic factors in controlling pituitary conversion of thyroxine (T4) to 3, 5, 3'-triiodothyronine (T3) via iodothyronine 5'-deiodination (I5'-D). Investigations will be conducted primarily utilizing the GH3 clonal rat pituitary tumor cell line. Preliminary experiments have documented the presence in this cell line of a two component I5'-I system which is very similar to that found in normal rat pituitary tissue and is responsive to a number of hormonal and metabolic perturbations. The specific aims of the project are: 1) to characterize the enzymatic processes responsible for T4 to T3 conversion in the GH3 clonal cell line; 2) to ascertain the effects of thyrotropin releasing hormone (TRH) and catecholamines on pituitary I5'-D; 3) to determine the physiologic importance of I5'-D in GH3 cells; and 4) to determine the cellular mechanisms whereby TRH and other neuropeptides influence I5'-D in GH3 cells. The proposed studies will provide new and important knowledge concerning the interrelationships between thyroid hormone and hypothalamic factors in the control of anterior pituitary gland function. The research opportunities available at the Dartmouth Medical School should provide an excellent environment for the further growth and development of the candidate's academic career. The primary sponsor is actively studying the mechanisms of thyroid hormone action and will thus be able to work closely with the candidate in achieving his research goals.